ID   BHMT2_MOUSE             Reviewed;         363 AA.
AC   Q91WS4; B1B1C9; Q8C1U2; Q9EQE8;
DT   23-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 2.
DT   02-SEP-2026, entry version 144.
DE   RecName: Full=S-methylmethionine--homocysteine S-methyltransferase BHMT2;
DE            Short=SMM-hcy methyltransferase;
DE            EC=2.1.1.10;
DE   AltName: Full=Betaine--homocysteine S-methyltransferase 2;
GN   Name=Bhmt2;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX   PubMed=11087663; DOI=10.1006/geno.2000.6319;
RA   Chadwick L.H., McCandless S.E., Silverman G.L., Schwartz S., Westaway D.,
RA   Nadeau J.H.;
RT   "Betaine-homocysteine methyltransferase-2: cDNA cloning, gene sequence,
RT   physical mapping, and expression of the human and mouse genes.";
RL   Genomics 70:66-73(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Gall bladder, and Liver;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=FVB/N; TISSUE=Kidney;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [5]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-321, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA   Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT   "Large-scale phosphorylation analysis of mouse liver.";
RL   Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN   [6]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=18230605; DOI=10.1074/jbc.m710449200;
RA   Szegedi S.S., Castro C.C., Koutmos M., Garrow T.A.;
RT   "Betaine-homocysteine S-methyltransferase-2 is an S-methylmethionine-
RT   homocysteine methyltransferase.";
RL   J. Biol. Chem. 283:8939-8945(2008).
RN   [7]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Kidney, and Liver;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
CC   -!- FUNCTION: Involved in the regulation of homocysteine metabolism.
CC       Converts homocysteine to methionine using S-methylmethionine (SMM) as a
CC       methyl donor. {ECO:0000269|PubMed:18230605}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=S-methyl-L-methionine + L-homocysteine = 2 L-methionine +
CC         H(+); Xref=Rhea:RHEA:26337, ChEBI:CHEBI:15378, ChEBI:CHEBI:57844,
CC         ChEBI:CHEBI:58199, ChEBI:CHEBI:58252; EC=2.1.1.10;
CC         Evidence={ECO:0000269|PubMed:18230605};
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC       Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC   -!- PATHWAY: Amino-acid biosynthesis; L-methionine biosynthesis via de novo
CC       pathway; L-methionine from L-homocysteine (BhmT route): step 1/1.
CC   -!- SUBUNIT: Homotetramer. {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: Expressed in fetal heart, lung, liver, kidney and
CC       eye. {ECO:0000269|PubMed:11087663}.
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DR   EMBL; AF257474; AAG41357.1; -; mRNA.
DR   EMBL; AK090308; BAC41163.1; -; mRNA.
DR   EMBL; AK145901; BAE26737.1; -; mRNA.
DR   EMBL; AC158524; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CT030023; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC013515; AAH13515.1; -; mRNA.
DR   CCDS; CCDS26689.1; -.
DR   RefSeq; NP_075022.2; NM_022884.2.
DR   AlphaFoldDB; Q91WS4; -.
DR   SMR; Q91WS4; -.
DR   FunCoup; Q91WS4; 263.
DR   STRING; 10090.ENSMUSP00000015941; -.
DR   iPTMnet; Q91WS4; -.
DR   PhosphoSitePlus; Q91WS4; -.
DR   SwissPalm; Q91WS4; -.
DR   jPOST; Q91WS4; -.
DR   PaxDb; 10090-ENSMUSP00000015941; -.
DR   PeptideAtlas; Q91WS4; -.
DR   ProteomicsDB; 273683; -.
DR   Antibodypedia; 24546; 116 antibodies from 22 providers.
DR   DNASU; 64918; -.
DR   Ensembl; ENSMUST00000015941.8; ENSMUSP00000015941.8; ENSMUSG00000042118.8.
DR   GeneID; 64918; -.
DR   KEGG; mmu:64918; -.
DR   UCSC; uc007rlk.1; mouse.
DR   AGR; MGI:1891379; -.
DR   CTD; 23743; -.
DR   MGI; MGI:1891379; Bhmt2.
DR   VEuPathDB; HostDB:ENSMUSG00000042118; -.
DR   eggNOG; KOG1579; Eukaryota.
DR   GeneTree; ENSGT00390000003122; -.
DR   HOGENOM; CLU_047457_0_0_1; -.
DR   InParanoid; Q91WS4; -.
DR   OMA; ENMESKW; -.
DR   OrthoDB; 261426at2759; -.
DR   PhylomeDB; Q91WS4; -.
DR   Reactome; R-MMU-1614635; Sulfur amino acid metabolism.
DR   UniPathway; UPA00051; UER00083.
DR   BioGRID-ORCS; 64918; 5 hits in 80 CRISPR screens.
DR   PRO; PR:Q91WS4; -.
DR   Proteomes; UP000000589; Chromosome 13.
DR   RNAct; Q91WS4; protein.
DR   Bgee; ENSMUSG00000042118; Expressed in left lobe of liver and 138 other cell types or tissues.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR   GO; GO:0047150; F:betaine-homocysteine S-methyltransferase activity; IEA:UniProtKB-ARBA.
DR   GO; GO:0008898; F:S-adenosylmethionine-homocysteine S-methyltransferase activity; ISO:MGI.
DR   GO; GO:0061627; F:S-methylmethionine-homocysteine S-methyltransferase activity; ISO:GO_Central.
DR   GO; GO:0008270; F:zinc ion binding; ISO:GO_Central.
DR   GO; GO:0071265; P:L-methionine biosynthetic process; ISO:MGI.
DR   GO; GO:0071267; P:L-methionine salvage; ISO:GO_Central.
DR   GO; GO:0046500; P:S-adenosylmethionine metabolic process; ISO:GO_Central.
DR   GO; GO:0033477; P:S-methylmethionine metabolic process; ISO:GO_Central.
DR   FunFam; 3.20.20.330:FF:000003; Betaine--homocysteine S-methyltransferase 1; 1.
DR   Gene3D; 3.20.20.330; Homocysteine-binding-like domain; 1.
DR   InterPro; IPR051524; BHMT.
DR   InterPro; IPR017226; BHMT-like.
DR   InterPro; IPR003726; HCY_dom.
DR   InterPro; IPR036589; HCY_dom_sf.
DR   PANTHER; PTHR46120; BETAINE--HOMOCYSTEINE S-METHYLTRANSFERASE 1; 1.
DR   PANTHER; PTHR46120:SF3; S-METHYLMETHIONINE--HOMOCYSTEINE S-METHYLTRANSFERASE BHMT2; 1.
DR   Pfam; PF02574; S-methyl_trans; 1.
DR   PIRSF; PIRSF037505; Betaine_HMT; 1.
DR   SUPFAM; SSF82282; Homocysteine S-methyltransferase; 1.
DR   PROSITE; PS50970; HCY; 1.
PE   1: Evidence at protein level;
KW   Metal-binding; Methyltransferase; Phosphoprotein; Reference proteome;
KW   Transferase; Zinc.
FT   CHAIN           1..363
FT                   /note="S-methylmethionine--homocysteine S-methyltransferase
FT                   BHMT2"
FT                   /id="PRO_0000273225"
FT   DOMAIN          11..305
FT                   /note="Hcy-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00333"
FT   BINDING         208
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00333"
FT   BINDING         290
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00333"
FT   BINDING         291
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00333"
FT   MOD_RES         321
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:17242355"
FT   CONFLICT        13
FT                   /note="I -> V (in Ref. 1; AAG41357)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        27
FT                   /note="S -> G (in Ref. 4; AAH13515)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        36
FT                   /note="R -> G (in Ref. 1; AAG41357)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        327
FT                   /note="N -> S (in Ref. 1; AAG41357)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   363 AA;  39872 MW;  C7367F1B10B07EEF CRC64;
     MAPAGSTRAK KGILERLDSG EVVVGDSGFL FTLEKRGFVK AGLWTPEAVV EHPSAVRQLH
     TEFLRAGADV LQTFTFSATE DNMASKWEAV NAAACDLAQE VAGGGGALVA GGICQTSLYK
     YHKDETRIKN IFRLQLEVFA RKNVDFLIAE YFEHVEEAVW AVEVLREVGA PVAVTMCIGP
     EGDMHDVTPG ECAVKLARAG ADIIGVNCRF GPWTSLQTMK LMKEGLRDAS LQAHLMVQCL
     GFHTPDCGKG GFVDLPEYPF GLEPRVATRW DIQKYAREAY NLGIRYIGGC CGFEPYHIRA
     IAEELAPERG FLPPASEKHG SWGSGLNMHT KPWIRARARR EYWENLLPAS GRPFCPSLSK
     PDA
//